The goal of the proposed research is the understanding of mechanisms underlying structural asymmetry of the brain and, ultimately, functional lateralization. Lateralization of neural structure and function is seen throughout the animal kingdom. In humans, the left hemisphere of most individuals is functionally specialized for linguistic tasks and the right for nonlinguistic tasks. The planum temporale, a language-related neuroanatomical area, is larger on the left in the majority of individuals. There is, however, significant individual variability in lateralization, especially among left-handers and nonright handers, who are more likely to show absence of asymmetry. Variability in brain asymmetry is also seen in nonhuman species, and, through the use of the rat as an experimental model, we intend to investigate histological, connectional, and developmental factors characterizing symmetry and asymmetry in the brain. The combined volume of homologous brain substrates in the two hemispheres decreases with increasing degree of asymmetry, and the asynmmetrical cases have fewer neurons on one side, rather than more neurons on the other. The question to be addressed in the first set of experiments is whether certain immunocytochemically identified neuronal subtypes are more involved than others in the production of this volume asymmetry. Thus, neurons that are immunocytochemically-reactive to each of four antibodies in specific architectonic areas of the cerebral cortex will be counted, their laminar distributions noted, and the findings will be related to volumetric asymmetry. The pattern and density of connections, in pilot studies, differ in brains with symmetrical and asymmetrical areas - symmetrical brains having a denser and more complex pattern of callosal terminations. The second set of experiments we will seek to replicate and extend these findings and to investigate whether this principle holds for thalamocortical connections, or whether the opposite is found since the two types of connections tend to be complementary. Specifically, the corpus callosum will be sectioned and the patterns of axonal termination in architectonic areas of the neocortex will be analyzed with respect to cerebral asymmetry and laminar location. In addition, the laminar and areal pattern of thalamocortical axonal terminals in the visual cortex of the rat will be examined after transneuronal transport of radioactive anterogade tracers injected into the eyes. In the third set of experiments, the ontogenetic processes underlying structural asymmetry will be examined. Pilot data do not point to asymmetry in rates of cell proliferation. Expanding on this study neocortical neurons labelled with [3H]Thymidine after injection during gestation will be counted in animals sacrificed at several postnatal ages. Analysis of these neuronal counts with respect to hemispheric asymmetry will help to determine whether neuronal count differences in asymmetrical and symmetrical brain areas relate to (1) the number of neurons in the original germinal zone or (2) developmental neuronal disappearance.